title: Anticancer therapy: boosting the bang of Bim.
abstract: Even though activating mutations of B-Raf, a kinase atop the MAPK signaling cascade, reportedly sensitize tumor cells to MEK inhibitors, Raf and MEK inhibitors have exhibited limited clinical activity. In this issue of the JCI, Cragg et al. report that MEK inhibition upregulates the proapoptotic Bcl-2 family member Bim but induces little regression of human melanoma xenografts in mice unless the Bcl-2 antagonist ABT-737 is added (see the related article beginning on page 3651). These findings illustrate the potential benefit of simultaneously inhibiting oncogenic kinases and inhibiting Bcl-2 action in solid tumors.
authors.affiliation: Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Andrea Wahner
authors.initials: AW
authors.lastname: Hendrickson
authors.forename: Xue Wei
authors.initials: XW
authors.lastname: Meng
authors.forename: Scott H
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D000072224:Bcl-2-Like Protein 11; D001713:Biphenyl Compounds; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D008954:Models, Biological; D009596:Nitrophenols; D010879:Piperazines; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D013449:Sulfonamides; D023041:Xenograft Model Antitumor Assays; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics
chemical_list: C501332:ABT-737; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D001713:Biphenyl Compounds; D008565:Membrane Proteins; D009596:Nitrophenols; D010879:Piperazines; D011518:Proto-Oncogene Proteins; D013449:Sulfonamides; D050998:bcl-2 Homologous Antagonist-Killer Protein; D048493:Proto-Oncogene Proteins B-raf; D020929:Mitogen-Activated Protein Kinase Kinases